17 Club de phase 1 meeting€¦ · Regulation n.1901/2006 & new tools: PaeDiatric COmmittee at the...

Paediatric Investigation Plans’ experience after

10 years: inclusion of the paediatric development

early is necessary when requested by regulation

17th Club de phase 1 meeting

Sylvie BENCHETRITFrench Delegate to the EMA PDCO

05/04/2018(slides from Paolo Tomasi, Gunter Egger)

1Agence nationale de sécurité du médicament et des produits de santé

Why is there a EU Paediatric Regulation?

Development of medicines for children: the EU experience1

=for

Security risks & communication

±

Off-label use


European Paediatric

Regulation n.1901/2006

&

new tools: PaeDiatric

COmmittee at the EMA

(PDCO) + PIPs

Population Definition

Children are NOT small adults

ICH E11 (R1) : age categories

preterm newborn infants (from day of birth to the expected date

of delivery plus 27 days)

term newborn infants (0 to 27 days, en discussion)

infants and toddlers (1 month (28 days) to 23 months)

"children" (2 to < 6 & 6 to < 12 years)

adolescents (12 to < 18 years)

Disease (“condition”/ MEDRA) and indication to be defined according to paediatric needs

To integrate in the paediatric development, according to appropiate

variables (ie. drug, disease, physio-pathology / relevant age-subset)


Population under « maturation » and

physiological development

Different in each age-stage, dev. not linear

Neonates: organs / maturation (kidney/liver, % fat, metabolism)

Infants, children: CNS, immunity, ….

Language, swallowing, motor dev. / walking

Bone growth, hormonal / sexual maturation & dev.

Adolescents : cognitive / psychosocial

Distinction to be done of relevant age-subsets to bedefined / BW-BSA

3rd dimension in drug evaluation


Disease knowledge recent and evolving(particularly in rare diseases)

Diseases are less known in children (ex: autism, migraine…)

Less consensus : scientific societes, WG, publications ongoing (ex:

ILAE definition of epileptic types/syndromes 2017, neonates seizures INC

2018, initial ages for inclusion vs first diagnosis discussed on orphan diseases;

methodological issues on small pop EMA WS 2017)

Scales for endpoints defined or revised continuously, to be validated

according to the ages of the patients under investigation (ex: QOL, MFM

vs 6MWT, 4SC in neuromuscular dystrophies, EVA – CHEOPS for pain, …)

Importance of published data on epidemiology, disease-registries (natural history), pb?, with data on dose, short and long-term efficacy and safety

Standardisation & validation of appropiate scales


Disease knowledge still variable

Less frequent:

Diseases only existing in children

Rare diseases, orphan (ex: genetic deficits with different phenotype /

age « subset », metabolic deficits)

Different aetiology / diagnostic / evolution in children (ex: chilhood

epilepsies, HTA, depression)

Different patient care (standard of care) / countries - centers:

Pharmacology investigation with innovative methods are necessary

Contraints of formulation / excipients, swallowing-school attendance

Faisability studies / design-timeline, paediatric networksEmpr-EMA


Paediatric Committee (PDCO)Delegates from European Union MSs (including paediatricians) +

Patients & academics representatives + EMA (paediatric coordinators)

+ alternates


From 2007, within EMA - key role in fulfilment of Paediatric Regulation

provisions (link with FDA, etc)

Main Tasks

Assess content of PIPs and requests for waivers/deferrals and

provide an opinion

Check compliance of an application with agreed PIPs

Provide advice on any question relating to paediatric medicines (at

the request of the Agency's Executive Director or the European

Commission) / WG + Scientific Advice + GL / WPs + PRAC ….

Supports EMA on the creation of a European network with

specific expertise in the performance of studies in the paediatric

population

The PDCO is not responsible for MAAs & Art. 45-46 review for products

for paediatric use, which is responsibility of the CHMP/CMDh NCAs

However, CHMP may request the PDCO to prepare an opinion on the quality,

safety and efficacy of a product if these data have been generated in

accordance with an agreed PIP

Paediatric Committee (PDCO)

| 8


9

Objectives of the Paediatric Regulation

Informations on paediatric drugs (even if MAA is

not granted)

Reports of a completed PIP (on all (non-)clinical

studies and quality maesures, except those

deferred)

Mandatory before the MAA submission request

Clinical studies in children according to GCP

Without non useful CS

And…not unnecessary delay of adult MAA


Paediatric

Investigation

Plan

(PIP)


PIP ? Document to frame the program of development of

medicinesto ensure their availability for children, from birth to less than 18 years of

age, in the requested indication (ie clinical symptomes)

Including the strategy and maesures / CS(s) synopis

Quality (age-appropiate formulation to be considered

from PK Ph1 Adults) and preclinical

Novel Notions on

medical need, to be considered earlier in the

development,

« waiver(s)» partial (per age subsets) or full

« deferral(s) » partial on initiation and/or completion

of CS-measures


Scope / PIP

Centralised, MRP/DC, national procedures

Mandatory before MAA (submission at end of ph1

when PK in adults in known, completion before

MAA)

New medicines (article 7) (irrespective of patent status)

Autorized / variation type 2 (art. 8) (with SPC -Supplementary

Protection Certificate - or patent qualifying for SPC)

Indication

Formulation ou route of administration

Exception of PUMA (art. 30): authorised off-patent drugs Volontary procedure

Only paediatric population


Not submitted to PIP obligation

Authorized products without a SPC or patent qualifying for SPC

Medicinal products authorised under Art 10 and 10(a) of Directive

2001/83/EC

Generics, hybrids, biosimilars and through the well-established

medicinal use procedure (“Usage bien établit”)

Medicinal products authorised under Art 13 to 16 of Directive

2001/83/EC

Homeopathic and herbal medicinal products

Attention: nevertheless, products impacted by other

aspects of the paediatric regulation, e.g., Article 46


EU Paediatric Regulation:

obligations versus incentives

Type of MP Obligation Incentive Comments

New#

Medicinal product

Paediatric Investigation Plan or Waiver

6 months extension of SPC (patent) *

Necessary for validation of application

On Patent and authorized

Medicine


6 months extension of SPC (patent)*

When new indication or new route or new pharmaceutical form:

necessary for validation

Orphan Medicine


2 additional years of market exclusivity*

In addition to 10 years

Off patent Medicine

None (voluntary PIP possible for PUMA)

10 years of data protection

Research funds

Paed. Use MA (PUMA)

*if compliance with PIP, information, approval EU-wide#according to GMA concept


PIP structure, Summary Report & PIP Opinion

A: Administrative, informations on the drug (PIP summary)

B: Clinical

- Disease, paediatric specifities vs adults

- Product Information (mode of action) et therapies-SOC

- Discussions therapeutic need/ drug

C: Waivers(s) full / partial

D: Developpement Strategy in children

- Available data (adults and children) and strategy of developpement (age

defined subsets, formulation, dose, E&S CS / PK-PD M&S /partial

extrapolation, timelines)

- Synopsis measures Q, Précl, Clin. « Opinion de PIP » binding

E: Deferral on initiation/completion of measures-CS

« Summary report PIP » = PIP D0 (& RfM D61) + comments Rapp,

Peer-R (coRapp), EMA coordinator minutes D30, D60, D90, D120 PDCO


Pediatric specifications / SmPC

- 4.1 indication or extension

- 4.2 new posology or amendement

- 4.3 ou 4.4 new pediatric information

- 4.8 nouvelle security data/results in pediatric CS

- 5.1 « waiver » or « deferral » to specify, ou new data

- 5.2 new data

- 5.3 new juvenile (non-clinical) data

→ Obligation to specify in the SmPC all the information

collected/analysed following the PIP developments / CS


PIP opinionPIP opinion template

1. waiver: condition

2. Paediatric investigation plan

2.1 condition – indication

Age subsets

Pharmaceutical form

Measures

Quality-related studies

Non-clinical studies

Clinical studies

Extrapolation, modelling and simulation studies

Other studies

Other measures

3. Follow-up, completion and deferral of PIP

4. Details of agreed measures

5. Potential long-term safety or efficacy issues for RMP/PV


Synopsis CS (cf. template PIP)

Clinical studies - Study identifier(s) (nb: «ongoing»)<Study number>

<Text>

Study design features and main objectives

Study population and subset definition

Number of study participants by paediatric subset (e.g. age,

sex, severity or stage)

Study duration for participants

Dosage, treatment regimen, route of administration

Control(s)

Primary endpoint(s) with time point(s) of assessment

Main secondary endpoint(s) with time(s) of assessment

Statistical plan including study conduct and analysis

Other

Plan for specific follow-up (not part of this study)

External Data Safety Monitoring Board

(Date of initiation)

Date of completion (last patient, last visit)


EMA/PDCO for PIP assessment

● EMA Paediatric Coordinator

• Contact person for the sponsor for the whole PIP procedure

• Provides critical review and coordinates the preparation of the summary report

● PDCO Rapporteur and Peer Reviewer

• Conducts critical review of the PIP

• Provides scientific expertise with comments of the Applicant’s PIP

• Identifies scientific issues and proposal for discussion by the Committee

● Working Groups: Formulation (FWG), Non-clinical (NcWG), MSWG

& EWG (other EMA committees, WG) (FDA pediatric clusters)

Summary report PIP (assessment) → PIP opinion (decision)

assessed by the PDCO

To be provided (SR PIP D120 + detailed opinion, ± D60

SR/opinion PIP modifications) for CS submission at ANSM


lkjbmjb

PIP nv ou modif.: 60 jours PIP RfM: 60 jours~ 3

months

Stop

Clock

Start

Clock

1st discussion

PDCO

D 30

2nd discussion

PDCO

D 60

(D61)

Applicant’s

answers

4rd discussion

(D120)

Opinion PIP

3rd discussion

PDCO

(D 90)

D0 after

validation

SR PIP

Possible

teleconf. Possible oral

explanation

Possible

teleconf.

Possible

teleconf.

Possible

teleconf.

Timelines PIP

Opinion D60

(for Full Waiver and

Modification PIP)

OR

D60 Request for

Modification of the PIP


Non-clin Phase 1 Phase 2 Phase 3

Initial PIP

MAA Review

PIP Modifications

PDCO

PIP Submission Timelines (SA / sc. Qs/ Eps)

MAA SubmissionCTA

CHMP

PIPCompliance Check

|

21

Sc. Ad

CTA CTA

Sc. Ad

SAWP SAWP


Timelines from PIP submission to SPC

expiry

Submission

of PIP

PIP

Review

(at least

150 days)EMA

Decision

on the PIP

Studies conducted in

accordance with PIP

(deferral granted)

(XX years)

Variation

Submission with

Paediatric data

Application of request

for the 6-month

extension to the SPC

At least 2 years before

SPC expiry

Expiry date

of the SPCEMA

Approval

of the

Adult MA

Initial MA

Submission in

adults

Applicant

EMA

|

22

Variation

approved


Compliance check request is to be done before submission of MA

application, exceptionally can also be conducted in parallel

In the latter case, validation is suspended until compliance is verified

The compliance request procedure will last 2-3 months

Letter of Intent (-1 month)

Compliance request submission

PDCO opinion within (30 or) 60 days of receiving the request

By the EMA-coordinator and the Rapporteur

If partial compliance, issue of a compliance report within 10 days

If final compliance Issue of a compliance report and opinion on compliance within 10 days

Compliance check is different than data assessment

"Yes" or "No" on the binding elements

No negotiation, no clock stop, no re-examination

Compliance Check on the agreed PIP

|

23


AntiEpileptic Drug development: time of dev.

on specific indications, driven by the adultADULT POP.

(symptomes)

Partial Onset

Seizures (focal)

PGTCS with IGE

PAEDIATRIC POP. (symptomes & types)

POS (focal) PGTCS with IGE

=> efficacy extrapolation? Ok ≥4 y. FDA –

EMA / Experts-Sg. Learning ociety (ILAE)

Epilepsy syndromes with generalized epilepsy

Chilhood types epilepsies ?

LGS, Dravet S, Infantile Spams,

TuberoSC, others

Neonatal seizures ?

Time of dev vs.

Patient

expiration

Partial

extrapolation

could allow

better

fulfulliment of

all needs

(chilhood

epilepsies /

neonatal

seizures can

be the most

severe ones)

Chiron,

Behrouz et al,

CNS Drugs

2013


« age appropiate formulation » development

Age-appropiate / size-shape of (mini-)tablets, oral

liquid < 6 y.

Composition: excipients

Acceptability / palatability: endpoint on CS

Volume(s) of administration, infusion rate

Device of accurate dosage

Waste of expensive drugs

Formulation Working Group (FWG) of PDCO

Guideline on pharmaceutical development of medicines for paediatric use 2014

Updated Excipients rec. (SWP)


Experiences with the EMA guideline on

pharmaceutical development of medicines for

paediatric use

University: mini-tablets / oral solution

517 patients 6 months - 6 years, Düsseldorf

Mini-tablets: 2 mm, coated or not

Versus syrup

Results :

At all ages, mini-tablets are better accepted vs oral solution

Little difference if coated or not

Well tolerated

Systems of maesure for counting mini-tablets exist.


Excipients labelling EMA

« Excipients in the label and package

leaflets of medicinal products for human

use » (CPMP/463/00) (PDCO, SWP, BWP, QWP, ..)

Updated information, thresolds

Paediatric population…

Including Q&A

Aspartame, benzyl alcohol, benzoic acid & benzoates,

benzalkonium chloride, gluten, boric acid, cyclodextrins,

ethanol, fragrance allergens, fructose and sorbitol,

phosphates, propylene glycol & esters, sodium

laurylsulfate & sodiumhttp://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document

_listing_000387.jsp&mid=WC0b01ac05808c01f6

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000387.jsp&mid=WC0b01ac05808c01f6


Pre-clinical development

Cf. non-clinical data on adults, ± available data /

Pharmacology: mode of action, safety

Pharmacokinetics

Toxicology: single and multiple doses, genotoxicity,

cancerogenicity, reprotoxicity (fertility, embryo-foetal

development , pre-post-natal dev.)...

→ dedicated studies in immature animal ?

Non Clinical Working Group (NcWG) of PDCO

Guideline on the need for non-clinical testing in juvenile

animals of pharmaceuticals for paediatric indications(EMEA/CHMP/SWP/169215/2005)

Oncology review: signals distincts from CS in adults, allowing to identify the

targets to monitor in CS


Specificities of Clinical Development

To integrate the paediatric development « asap, end Ph1 », and by age-subsets From end of pharmacokinetic studies in adults

Design of the CS with rationale/justification:

Dose regimen determination: PK/PD CS / IA for confirmation (M&S

& extrapolation)

Selection and validation of efficacy criteria (ex: DMD, Depression)

Selection of traitement /control (placebo or SOC ? < 2 y?)

Folllow up monitoring - Pharmacovigilance (>2-5 y?)

Faisability and appropiate recruitment : selection of « paediatric »

centres

Objective: MAA

ie EMA website: paed. Workshops-expert meetings-Scientific

guidelines, EMA publications and PIP/M&S/Extr. templates


PK-PD in children

Volumes & timepoints blood sampling CS:

guideline EC 2008 "ethical considerations for clinical trials on medicinal products conducted with the pediatric population”

limites

3 % of total blood volume (BV) during a period of 4 weeks

1 % BV at any single time

BV ~ 80 to 90 ml/kg body weight 3% ~ 2,4 ml

Pharmacodynamic markers Need of appropiate PD markers, comparative data from Adults

CS or other paediatric CS is useful (dose rationale)

Sparse sampling / Population PK/PK-PD – PBPK

Sensitive assays / micro-sampling techniques (<0.5 - 1 ml)

PD to be considered from Ph1-Ph2


4A 3A7 2D6 2E13A53A42C 2B6

2A6

1A2 F<30w

F>30w

<24h1-7d

8-28d

1-3m3-12m

>1y

adults

Age-based changes in CYP activityfrom Cresteil, Food Add Cont, 15:45, 1996


Modelling & Simulation + Extrapolation :

optimizing dose & designs

Innovative methods M&S combined, with all data available

(including other indications), to identify the initial dose in children

Pop PK & PD - Bayesian

PBPK & PD – Systems pharmacology (< 2 y. particularly)

PKPD studies or Ph3 / adaptative design

Validation of predicted PK/PD dose – E – S

Real data, process to be updated (design, interim analysis)

→ GL framework : dose-finding workshops (M&S/Extrapolation WG),

GL extrapolation EMA, FDA ped. pharmacology 2015 EMEA/CHMP/EWP/147013/2004 Corrigendum Guideline on the role of pharmacokinetics in the development of medicineal products in the paediatric

population

EMA/CHMP/458101/2016 Guideline on the qualification and reporting of physiologically based pharmacokinetic (PBPK) modelling and simulation

EMA/178564/2017 Reflection paper on the use of quantitative tools for extrapolation in paediatric medicines development

EMA/199678/2016 Reflection paper on extrapolation of efficacy and safety in paediatric medicine development


Paediatric clinical trials

10-year Report to EC on the Paediatric Regulation

Source: EudraCT database

9,3%

8,2%

8,9%

9,8%

10,8%

10,5%

10,0%

10,2%

10,0%

11,5%

8%

9%

9%

10%

10%

11%

11%

12%

12%

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

% of paediatric trials(of all trials, by start year)

paediatric trial: any trial that allows inclusion of patients 0-18 yo


High-quality paediatric research

• More than 700 PIPs are ongoing

• ~100 PIPs have been completed

• Support across European network for paediatric matters

and collaboration of committees / working parties /

working groups (CHMP, PDCO, PRAC, COMP, CAT,

SAWP, MSWG, FWG, NCWG, CMDh)

Systematic review of paediatric developments



Context Delays in completion and results reporting of clinical trials under the

Paediatric Regulation in the European Union: A cohort study 2010-2014

(Thomas J. Hwang, Paolo A. Tomasi, Florence T. Bourgeois) Plos medicine March 2018

PLoS Med 15 (3): e1002520. https://doi.org/10.1371/journal.pmed.1002520

326 paediatric clinical trials for 122 novel medicines authorised by the EMA

76% (247/326) of paediatric studies not planned to be completed at initial MA

Rate of completion CS : 23% (56/247) for those planned completed after MAA vs 86% (68/79)

for trials planned to be completed before authorisation (adjusted hazard ratio 0.11; 95% CI

0.06±0.19).

Completion dates for 50% (162/326) postponed by a median of 2.2 year

38% (124/326) of paediatric studies completed as of 30 November 2017

Among completed studies, publication reported in a public registry or in the peer-reviewed

literature for 85% (105/124) at a median of 1.1 y. after study completion, and 60% (74/124)

were published in a peer-reviewed journal

(Limitations: medicines not authorised by the EMA and possible trials to be completed or

published in the future)

https://doi.org/10.1371/journal.pmed.1002520


FDA

Best Pharmaceutical for Children Act

(BPCA) 1997

Pediatric Research Equity Act (PREA)

2003

Pediatric Study Plans, 2012/13, to

be submitted early in the dev.http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm360507.pdf

Research to Accelerate Cures and

Equity for Children Act (RACE) 2017requires companies developing targeted cancer drugs for adults to

develop those drugs for children with cancer as well

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm360507.pdf


Thank you

http://ansm.sante.fr/Activites/Medicaments-en-pediatrie

http://ansm.sante.fr/Activites/Medicaments-en-pediatrie


Differences EU (Paediatric Regulation) /

USA (BPCA-PREA-FDAAA)US BPCA (Best

Pharmaceutical for

Children Act) 1997

US PREA (Pediatric

Research Equity Act)

2003

EU 2006

Development Optional Mandatory Mandatory(optional for off-patent)

Instrument Written Request Paediatric Study Plan (PSP, 2012) if deferral

Paediatric Investigation Plan (PIP)

Waiver N/A 3 grounds 3 grounds

Timing End of phase 2 End of phase 2 End of phase 1

Reward 6 months exclusivity

- Main: 6 months SPC extension (patent)

New drugs (section 505)

YesWith exclusivity

Yes Yes

Biologicals (most)

Yes All All

Orphan Included Excluded Included

Decision FDA FDA EMA(Opinion: PDCO)


Paediatric workshopshttp://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000416.jsp&mid=WC0b01ac058

0925cc6

2017

FP7 Small-population research methods projects and regulatory application workshop (29-30 March 2017)

2016

European Medicines Agency public workshop on extrapolation of efficacy and safety in medicine development (17-

18/05/2016)

European Medicines Agency-Industry stakeholders Platform second meeting on paediatric medicines (15/04/2016)

2015

European network of paediatric research-European Medicines Agency meeting on rare gastrointestinal and liver

diseases (08/12/2015)

Expert meeting on paediatric development of fixed-dose combinations for the treatment of the human

immunodeficiency virus (HIV) (10/11/2015)

European Medicines Agency workshop on extrapolation across age groups (30/09/2015)

Applying regulatory science to neonates: launch of the International Neonatal Consortium (INC) (18-19/05/2015)

European Medicines Agency-industry stakeholders platform meeting on paediatric medicines (11/05/2015)

Collaboration on neonatal issues between researchers and the European Medicines Agency (17/03/2015)

2014

Expert meeting on the clinical investigation of medicines for the treatment of paediatric hepatitis C (09/12/2014)

Paediatric osteoporosis expert meeting (02/06/2014)

Pharmacovigilance in the paediatric population workshop (28/04/2014)

2013

Workshop on paediatric investigation plans in type-2 diabetes mellitus (25/02/2013)

2012

Paediatric anticoagulation therapy expert meeting (06/11/2012)

Joint European Medicines Agency / Food and Drug Administration workshop for paediatric Gaucher disease type I:

exploring the way forward (17-18/10/2012)

Workshop on endpoints for cystic fibrosis clinical trials (27-28/09/2012)

http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/events/2015/10/event_detail_001230.jsp&mid=WC0b01ac058004d5c3
















Scientific guidelines: paediatrics

Quality / Non-clinical / Clinical E & S / etchttp://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_co

ntent_000404.jsp&mid=WC0b01ac0580029572

•Clinical evaluation of medicinal products used in weight control - addendum on weight control in children

•Clinical investigation of medicinal products for the treatment of Duchenne and Becker muscular dystrophy

•Clinical trials in small populations

•Conduct of pharmacovigilance for medicines used by the paediatric population

•Evaluation of anticancer medicinal products in man - addendum on paediatric oncology

•ICH E11 Clinical investigation of medicinal products in the paediatric population

•Investigation of medicinal products in the term and preterm neonate

•Paediatric addendum on the CHMP guideline on clinical investigation of medicinal products for the treatment of acute heart

failure

•Paediatric addendum to the guideline on clinical investigation on medicinal products in the treatment of hypertension

•Paediatric addendum to the guideline on clinical investigation of medicinal products in the treatment of lipid disorders

•Paediatric addendum to the guideline on clinical investigation of medicinal products for the treatment of pulmonary arterial

hypertension

•Role of pharmacokinetics in the development of medicinal products in the paediatric population

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_001028.jsp&mid=WC0b01ac0580032ec6

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_001166.jsp&mid=WC0b01ac0580034cf5

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_001224.jsp&mid=WC0b01ac05807d91a4

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_001333.jsp&mid=WC0b01ac0580029572

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_001129.jsp&mid=WC0b01ac0580034cf3

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_001256.jsp&mid=WC0b01ac0580032ec4


http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_001088.jsp&mid=WC0b01ac0580034cef






More information on paediatric medicines

Article 45 assessments• Nationally authorised medicines: 219

• Centrally authorised medicines: 62

~140 SmPC updates

16 new paediatric indications (including in areas where no

paediatric medicines were approved.)

Article 46 assessments• Nationally authorised medicines: 80

• Centrally authorised medicines: 280

~90 SmPC updates (incl. paed. ind. for leuporelin acetate)


Avertissement

• Lien d’intérêt : personnel salarié de l’ANSM (opérateur de l’Etat).

• La présente intervention s’inscrit dans un strict respect d’indépendance et

d’impartialité de l’ANSM vis-à-vis des autres intervenants.

• Toute utilisation du matériel présenté, doit être soumise à l'approbation

préalable de l’ANSM.

Warning

• Link of interest: employee of ANSM (State operator).

• This speech is made under strict compliance with the independence and

impartiality of ANSM as regards other speakers.

• Any further use of this material must be submitted to ANSM prior approval.

17 Club de phase 1 meeting€¦ · Regulation n.1901/2006 & new tools: PaeDiatric COmmittee at the...

Documents

Transcript of 17 Club de phase 1 meeting€¦ · Regulation n.1901/2006 & new tools: PaeDiatric COmmittee at the...